thromboxane-a2 and Renal-Artery-Obstruction

Recent studies have reported elevated prostaglandin levels in patients with renal artery stenosis and hypertension. To investigate whether a distinction between essential hypertension and hypertension with renal artery stenosis is possible by measuring eicosanoid excretion, we studied the excretion of these compounds in patients with essential hypertension and in hypertensives with concomitant renal artery stenosis.. The 24-h urinary excretion of metabolites of prostaglandin I2, prostaglandin E2 and metabolites of thromboxane A2 was sampled under standardised conditions, in 15 patients with essential hypertension and in 15 patients with unilateral renal artery stenosis with hypertension. Also clinical and biochemical characteristics of the subjects were analysed.. The patients with renal artery stenosis had significantly lower excretion of prostaglandin I2 than did the essential hypertensive patients. However, the overlap in the values was large, thus not allowing a diagnostic differentiation according to urinary prostaglandin I2 levels. The excretion of prostaglandin E2 and of metabolites of thromboxane A2 showed no significant differences among the groups.. Measurement of urinary prostaglandin or prostaglandin metabolite excretion did not contribute to the non-invasive detection of the presence of a renal artery stenosis in the patients in this study.

Topics: Adult; Aged; Dinoprostone; Epoprostenol; Female; Humans; Hypertension; Hypertension, Renovascular; Logistic Models; Male; Middle Aged; Renal Artery Obstruction; Thromboxane A2

The effect of the thromboxane (Tx) A2-receptor antagonists SQ 28,668 and SQ 30,741 on platelet function and renal artery thrombosis was studied in the dialurethane-anesthetized cynomolgus monkey. Both antagonists competitively inhibited the aggregation of platelet rich plasma in vitro to arachidonic acid and U-46,619, a Tx-mimetic. SQ 30,741 was 4 to 7 times more potent than SQ 28,668 against either of these agonists. Thrombotic cyclical blood flow reductions (CFRs) were elicited by placing a critical stenosis at a crush injury site on the left renal artery. After allowing 10 consecutive CFRs, of which 95% required shaking of the vessel to restore flow, a single i.v. injection of either SQ 28,668 (1 mg/kg, n = 6), SQ 30,741 (1 mg/kg, n = 8) or vehicle (2 ml of 0.2% Na2CO3 + 10% ethanol, n = 4) was administered. Antithrombotic activity was defined as the spontaneous restoration of flow and was accompanied by a reduction in the rate of flow decline during the CFRs. Spontaneous flow restoration was observed in animals treated with SQ 28,668 (five of six) and SQ 30,741 (six of eight) but not vehicle (zero of four). The rate of flow decline was reduced only with SQ 28,668 (56 +/- 8%) and SQ 30,741 (53 +/- 10%) treatments. The antithrombotic activities of SQ 28,668 and SQ 30,741 lasted 68 +/- 6 and 224 +/- 21 min, respectively. The threshold antithrombotic dose was found to be lower for SQ 30,741 (0.20 +/- 0.03 mg/kg) than SQ 28,668 (0.61 +/- 0.09 mg/kg) in additional experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Dose-Response Relationship, Drug; Ketanserin; Macaca fascicularis; Platelet Aggregation; Receptors, Prostaglandin; Receptors, Thromboxane; Renal Artery Obstruction; Renal Circulation; Thrombosis; Thromboxane A2